It is known to use a compressed fluid, typically a supercritical or near-critical fluid, as an anti-solvent to precipitate particles of a substance of interest (a “target substance”) from solution or suspension. The basic technique is known as “GAS” (Gas Anti-Solvent) precipitation [Gallagher et al, “Supercritical Fluid Science and Technology”, ACS Symp. Ser., 406, p334 (1989)]. Versions of it have been disclosed for instance in EP-0 322 687 and WO-90/03782, which are hereby incorporated in their entirety by reference.
In one particular version known as SEDS™ (Solution Enhanced Dispersion by Supercritical fluids), a target substance is dissolved or suspended in an appropriate fluid vehicle, and the resulting “target solution/suspension” then co-introduced into a particle formation vessel with an anti-solvent fluid (usually supercritical) in which the vehicle is soluble. The co-introduction is effected in a particular way, such that:                the target solution/suspension and the anti-solvent both meet and enter the vessel at substantially the same point; and        at that point, the mechanical energy of the anti-solvent serves to disperse the target solution/suspension (i.e., to break it up into individual fluid elements) at the same time as the anti-solvent extracts the vehicle so as to cause particle formation.        
Thus, in SEDS™, the compressed fluid serves not only as an anti-solvent but also as a mechanical dispersing agent. The simultaneity of fluid contact, dispersion and particle formation provides a high degree of control over the physicochemical properties of the particulate product.
Versions of SEDS™ are described in WO-95/01221, WO-96/00610, WO-98/36825, WO-99/44733, WO-99/59710, WO-01/03821, WO-01/15664 and WO-02/38127. Other SEDS™ processes are described in WO-99/52507, WO-99/52550, WO-00/30612, WO-00/30613 and WO-00/67892, all of which are hereby incorporated in their entirety by reference
Another version of the GAS technique is described in WO-97/31691, in which a special form of two-fluid nozzle is used to introduce a “target solution/suspension” and an energising gas into a particle formation vessel containing a supercritical anti-solvent. The energising gas can be the same as the anti-solvent fluid. Within the nozzle, a restriction generates sonic waves in the energising gas/anti-solvent flow and focusses them back (i.e., in a direction opposite to that of the energising gas flow) on the outlet of the target solution/suspension passage, resulting in mixing of the fluids within the nozzle before they enter the particle formation vessel. It is suggested that where the energising gas is the same as the anti-solvent (typically supercritical carbon dioxide), its flow rate could be sufficiently high to obtain a sonic velocity at the nozzle outlet. However, the authors do not appear ever to have achieved such high velocities in their experimental examples.
Other modifications have been made to the basic GAS process in order to affect atomisation of the target solution/suspension at the point of its contact with the compressed fluid anti-solvent. For example, U.S. Pat. No. 5,770,559 describes a GAS precipitation process in which a target solution is introduced, using a sonicated spray nozzle, into a pressure vessel containing a supercritical or near-critical anti-solvent fluid—see also Randolph et al in Biotechnol. Prog., 1993, 9, 429–435.
It would be generally desirable to provide alternative particle formation techniques which combined one or more of the advantages of the prior art methods with a broader applicability (for instance, for a wider range of target substances, vehicles and/or anti-solvents) and/or a higher degree of control over the product characteristics. In particular it is generally desirable, especially for pharmaceutical substances, to be able to produce small (even sub-micron) particles with narrow size distributions.